The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
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DOI：
10.1038/ng959
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发表时间：
2002-09-01
期刊：
影响因子：
30.8
通讯作者：
Wright, CVE
中科院分区：
文献类型：
--
作者：
Kawaguchi, Y;Cooper, B;Wright, CVE
胰腺的发育始于胚胎前肠内胚层特定部位的芽的形成。我们使用基于重组的体内谱系追踪来显示Ptf 1a（也称为PTF 1-p48）在胰腺导管、外分泌和内分泌细胞的祖细胞中的这些早期阶段表达，而不是如先前所述的作为外分泌特异性基因。此外，Ptf 1a的失活改变了胰腺祖细胞的特征，使其后代在十二指肠上皮细胞（包括其干细胞区室）中增殖并采用正常的命运。与Ptf 1a支持所有三种胰腺细胞类型的前体的规范的提议一致，Pdx 1（胰腺形成所必需的基因）的转基因表达从Ptf 1a顺式调节序列将胰腺组织恢复到Pdx 1缺失小鼠，否则由于器官发生的早期停滞而缺乏成熟的外分泌和内分泌细胞。这些实验提供的证据表明，Ptf 1a的表达是专门连接到胰腺的命运收购未分化的前肠内胚层。
Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described. Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.